The Dopamine System in Mediating Alcohol Effects in Humans

  • K. CharletEmail author
  • A. Beck
  • A. Heinz
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 13)


Recent brain–imaging studies revealed that the development and maintenance of alcohol dependence is determined by a complex interaction of different neurotransmitter systems and multiple psychological factors. In this context, the dopaminergic reinforcement system appears to be of fundamental importance. We focus on the excitatory and depressant effects of acute versus chronic alcohol intake and its impact on dopaminergic neurotransmission. Furthermore, we describe alterations in dopaminergic neurotransmission as associated with symptoms of alcohol dependence. We specifically focus on neuroadaptations to chronic alcohol consumption and their effect on central processing of alcohol-associated and reward-related stimuli. Dysfunctional reward processing, impaired reinforcement learning and increased salience attribution to alcohol-associated stimuli enable alcohol cues to drive alcohol seeking and consumption. Finally, we will discuss how the neurobiological and neurochemical mechanisms of alcohol-associated alterations in reward processing and learning can interact with personality traits, cognition and emotion processing.


Dopamine Acute alcohol effects Chronic alcohol effects Imaging Cue-reactivity Reward system 

List of Abbreviations




Anterior cingulate cortex


α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors


Blood alcohol concentration


Blood oxygen level dependent response


Central nervous system


Pavlovian conditioned stimulus




Dorsolateral prefrontal cortex


Dopamine D1 receptor


Dopamine D2 receptor


Dopamine D3 receptor


Diffusion tensor imaging






Functional magnetic resonance imaging




Gamma-aminobutyric acid


Harm Avoidance


International Affective Picture System


Long-term potentiation


Medial prefrontal cortex


Nucleus accumbens




Novelty Seeking


Orbitofrontal cortex


Positron emission tomography


Prefrontal cortex


Single photon emission computed tomography


Statistical Parametric Mapping


Selective serotonin reuptake inhibitors


T1-Weighted magnetic resonance sequence


Cloningers Tridimensional Personality Questionnaire (Cloninger 1987b)


Ventral tegmental area


Working memory



This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft; HE 2597/4-3; 7-3; EXC257), by the Bernstein Center for Computational Neuroscience Berlin (BMBF grant 01GQ0411) and NGFN (BMBF grant 01GS08159).


  1. Adermark L, Clarke R, Olsson T, Hansson E, Söderpalm B, Ericson E (2010) Implications for glycine receptors and astrocytes in ethanol-induced elevation of dopamine levels in the nucleus accumbens. Addict BiolGoogle Scholar
  2. Aneshensel C, Huba G (1983) Depression, alcohol use, and smoking over one year: a four-wave longitudinal causal model. J Abnorm Psychol 92:134–150PubMedGoogle Scholar
  3. Ase A, Reader T, Hen R, Riad M, Descarries L (2000) Altered serotonin and dopamine metabolism in the CNS of serotonin 5-HT(1A) or 5-HT(1B) receptor knockout mice. J Neurochem 75:2415–2426PubMedGoogle Scholar
  4. Barratt E (1982) Impulsivity, Behavioral Dyscontrol, and Conscious Awareness. Behav mot control psychiatr disord S04:217Google Scholar
  5. Begleiter H, Porjesz B (1999) What is inherited in the predisposition toward alcoholism? A proposed model. Alcohol Clin Exp Res 23:1125–1135PubMedGoogle Scholar
  6. Berke J, Hyman S (2000) Addiction, dopamine, and the molecular mechanisms of memory. Neuron 25:515–532PubMedGoogle Scholar
  7. Berridge K, Kringelbach M (2008) Affective neuroscience of pleasure: reward in humans and animals. Psychopharmacology 199:457–480PubMedCentralPubMedGoogle Scholar
  8. Berridge K, Robinson T, Aldridge J (2009) Dissecting components of reward: ‘liking’, ‘wanting’, and learning. Curr Opin Pharmacol. 9:65–73PubMedCentralPubMedGoogle Scholar
  9. Birbaumer N, Schmidt R (2003) Biologische Psychologie. 5. Auflage. Springer-Verlag, Springer-VerlagGoogle Scholar
  10. Bishop M, Elder S, Heath R (1963) Incranial self-stimulation in man. Science 140:394–396PubMedGoogle Scholar
  11. Blum K, Sheridan P, Wood R, Braverman E, Chen T, Cull J, Comings D (1996) The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. J R Soc Med 89:396–400PubMedCentralPubMedGoogle Scholar
  12. Boileau I, Assaad J, Pihl R, Benkelfat C, Leyton M, Diksic M, Trembley R, Dagher A (2003) Alcohol Promotes Dopamine Release in the Human Nucleus Accumbens. Synapse 49:226–231PubMedGoogle Scholar
  13. Bowirrat A, Oscar-Berman M (2005) Relationship Between Dopaminergic Neurotransmission, Alcoholism, and Reward Deficiency Syndrome. American Journal of Medical Genetics Part B (Neuropsychiatric Genetics) 132B:29–37Google Scholar
  14. Braus DF, Wrase J, Grüsser SM, Hermann D, Ruf M, Flor H (2001) Alcohol-associated stimuli activate the ventral striatum in abstinent alcoholics. J Neural Transm 108:887–894PubMedGoogle Scholar
  15. Brumback T, Cao D, King A (2007) Effects of alcohol on psychomotor performance and perceived impairment in heavy binge social drinkers. Drug Alcohol Depend 91:10–17PubMedCentralPubMedGoogle Scholar
  16. Bushman B, Cooper H (1990) Effects of alcohol on human aggression: an integrative research review. Psychol Bull. 107:341–354PubMedGoogle Scholar
  17. Carlson R, Lydic R (1976) The Effect of ethanol upon Threshold and Response Rate for Self-Stimulation. Psychopharmacology 50:61–64PubMedGoogle Scholar
  18. Carlsson A, Engel J, Strömbom U, Svensson T, Waldeck B (1974) Suppression by dopamine-agonists of the ethanol-induced stimulation of locomotor activity and brain dopamine synthesis. Naunyn Schmiedebergs Arch Pharmacol 283:117–128PubMedGoogle Scholar
  19. Carter B, Tiffany S (1999) Meta-analysis of cue-reactivity in addiction research. Addiction 94:327–340PubMedGoogle Scholar
  20. Cloninger C (1987a) Neurogenetic adaptive mechanisms in alcoholism. Science 236:410–416PubMedGoogle Scholar
  21. Cloninger C (1987b) A systematic method for clinical description and classification of personality variants: a proposal. Arch Gen Psychiatry 44:573–588PubMedGoogle Scholar
  22. Cohen C, Perrault G, Sanger D (1997) Evidence for the involvement of dopamine receptors in ethanol-induced hyperactivity in mice. Neuropharmacology 36:1099–1108PubMedGoogle Scholar
  23. Crabbe JC, Bell RL, Ehlers CL (2010) Human and laboratory rodent low response to alcohol: is better consilience possible? Addict Biol 15(2):125–144PubMedCentralPubMedGoogle Scholar
  24. Crews F, Buckley T, Dodd P, Ende G, Foley N, Harper C, He J, Innes D, Loh E-W, Pfefferbaum A, Zou J, Sullivan E (2005) Alcoholic neurobiology: Changes in dependence and recovery. Alcoholism: Clinical and Experimental Research 29:1504–1513Google Scholar
  25. Dayas C, Liu X, Simms J, Weiss F (2007) Distinct patterns of neural activation associated with ethanol seeking: effects of naltrexone. Biol Psychiatry 61:979–989PubMedCentralPubMedGoogle Scholar
  26. de Waele J, Kiianmaa K, Gianoulakis C (1994) Spontaneous and ethanol-stimulated in vitro release of beta-endorphin by the hypothalamus of AA and ANA rats. Alcohol Clin Exp Res 18:1468–1473PubMedGoogle Scholar
  27. de Wit H, Uhlenhuth E, Pierri J, Johanson C (1987) Individual differences in behavioral and subjective responses to alcohol. Alcohol Clin Exp Res 11:52–59PubMedGoogle Scholar
  28. de Wit H, Pierri J, Johanson C (1989) Assessing individual differences in ethanol preference using a cumulative dosing procedure. Psychopharmacology 98:113–119Google Scholar
  29. Di Chiara G (2002) Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 137:75–114PubMedGoogle Scholar
  30. Di Chiara G, Bassareo V (2007) Reward system and addiction: what dopamine does and doesn’t do. Curr Opin Pharmacol. 7:69–76PubMedGoogle Scholar
  31. Di Sclafani V, Ezekiel F, Meyerhoff D, MacKay S, Dillon W, Weiner M, Fein G (1995) Brain atrophy and cognitive function in older abstinent alcoholic men. Alcoholism: Clinical and Experimental Research 19:1121–1126Google Scholar
  32. Dougherty D, Marsh-Richard D, Hatzis E, Nouvion S, Mathias C (2008) A test of alcohol dose effects on multiple behavioral measures of impulsivity. Drug Alcohol Depend 96:111–120PubMedCentralPubMedGoogle Scholar
  33. Drogenbeauftragte der Bundesregierung (2009) Drogen- und Suchtbericht Mai 2009. Bundesministerium für Gesundheit. Berlin, GermanyGoogle Scholar
  34. Drummond D (2000) What does cue-reactivity have to offer clinical research? Addiction 95:129–144Google Scholar
  35. Duka T, Tasker R, Stephens D (1998) Alcohol choice and outcome expectancies in social drinkers. Behav Pharmacol 9:643–653PubMedGoogle Scholar
  36. Egan M, Goldberg T, Kolachana B, Callicott J, Mazzanti C, Straub R, Goldman D, Weinberger D (2001) Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A 98:6917–6922PubMedCentralPubMedGoogle Scholar
  37. Ekman G, Frankenhaeuser M, Goldberg L, Bjerver K, Jarpe G, Myrsten A (1963) Effects of alcohol intake on subjective and objective variables over a five-hour period. Psychopharmacologia 4:28–38PubMedGoogle Scholar
  38. Ekman G, Frankenhaeuser M, Goldberg L, Hagdahl R, Myrsten A (1964) Subjective and objective effects of alcohol as functions of dosage and time. Psychopharmacologia 6:399–409PubMedGoogle Scholar
  39. Fillmore M, Weafer J (2004) Alcohol impairment of behavior in men and women. Addiction 99:1237–1246PubMedGoogle Scholar
  40. Fillmore M, Marczinski C, Bowman A (2005) Acute tolerance to alcohol effects on inhibitory and activational mechanisms of behavioral control. J Stud Alcohol 66:663–672PubMedGoogle Scholar
  41. Finn P, Sharkansky E, Brandt K, Turcotte N (2000) The effects of familial risk, personality, and expectancies on alcohol use and abuse. J Abnorm Psychol 109:122–133PubMedGoogle Scholar
  42. Frigerio E, Burt D, Montagne B, Murray L, Perrett D (2002) Facial affect perception in alcoholics. Psychiatry Research 113:161–171PubMedGoogle Scholar
  43. Fromme K, Katz E, D’Amico E (1997) Effects of alcohol intoxication on the perceived consequences of risk taking. Exp Clin Psychopharmacol 5:14–23PubMedGoogle Scholar
  44. Garavan H, Pankiewicz J, Bloom A, Cho J, Sperry L, Ross T, Salmeron B, Risinger R, Kelley D, Stein E (2000) Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. Am J Psychiatry 157:1789–1798PubMedGoogle Scholar
  45. Garbutt JC, West SL, Carey TS, Lohr KN, Crews FT (1999) Pharmacological treatment of alcohol dependence: a review of the evidence. JAMA 281(14):1318–1325PubMedGoogle Scholar
  46. Gardner E (2005) Endocannabinoid signaling system and brain reward: Emphysis on dopamine. Pharmacol Biochem Behav 81:263–284PubMedGoogle Scholar
  47. George MS, Anton RF, Bloomer C, Teneback C, Drobes DJ, Lorberbaum JP, Nahes Z, Vincent DJ (2001) Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues. Arch Gen Psychiatry 58:345–352PubMedGoogle Scholar
  48. Giancola P, Zeichner A (1997) The biphasic effects of alcohol on human physical aggression. J Abnorm Psychol 106:598–607PubMedGoogle Scholar
  49. Gilman J, Ramchandani V, Davis M, Bjork J, Hommer D (2008) Why we like to drink: A functional magnetic resonance imaging study of the rewarding and anxiolytic effects of alcohol J Neurosci 28:4583–4591Google Scholar
  50. Glenn S, Parsons O (1991) Prediction of resumption of drinking in posttreatment alcoholics. Int J Addict 26:237–254PubMedGoogle Scholar
  51. Goldman-Rakic P (1995) Cellular basis of working memory. Neuron 14:477–485PubMedGoogle Scholar
  52. Gorelick D (1989) Serotonin uptake blockers and the treatment of alcoholism. Recent Dev Alcohol 7:267–281PubMedGoogle Scholar
  53. Goto Y, Grace A (2005) Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior. Nat Neurosci 8:805–812PubMedGoogle Scholar
  54. Grace A, Floresco S, Goto Y, Lodge D (2007) Regulation of dopamine neuron firing and the control of goal-directed behaviors. Trends in Neurosciences 30:220–227PubMedGoogle Scholar
  55. Grillon C, Sinha R, O’Malley S (1995) Effects of ethanol on the processing of low probability stimuli: an ERP study. Psychopharmacology 119:455–465PubMedGoogle Scholar
  56. Grüsser S, Wrase J, Klein S, Hermann D, Smolka M, Ruf M, Weber-Fahr W, Flor H, Mann K, Braus D, Heinz A (2004) Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology 175:296–302PubMedGoogle Scholar
  57. Hansson AC, Nixon K, Rimondini R, Damadzic R, Sommer WH, Eskay R, Crews FT, Heilig M (2010) Long-term suppression of forebrain neurogenesis and loss of neuronal progenitor cells following prolonged alcohol dependence in rats. Int J Neuropsychopharmacol 13:583–593PubMedGoogle Scholar
  58. Harris G, Oscar-Berman M, Gansler A, Streeter C, Lewis R, Ahmed I, Achong D (1999) Hypoperfusion of cerebellum and aging effects on cerebral cortex blood flow in abstinent alcoholics: A SPECT study. Alcoholism: Clinical and Experimental Research 23:1219–1227Google Scholar
  59. Heath R (1963) Electrical self-stimulation of the brain in man. Am J Psychiatry 120:571–577PubMedGoogle Scholar
  60. Heinz A (2000) Das dopaminerge Verstärkungssystem. Funktion, Interaktion mit anderen Neurotransmittersystemen und psychopathologische Korrelate. Steinkopff Verlag, Steinkopff VerlagGoogle Scholar
  61. Heinz A, Schmidt L, Reischies F (1994) Anhedonia in schizophrenic, depressed, or alcohol-dependent patients: neurobiological correlates. Pharmacopsychiatry 27(suppl):7–10PubMedGoogle Scholar
  62. Heinz A, Dettling M, Kuhn S, Dufeu P, Gräf K, Kürten I, Rommelspacher H, Schmidt I (1995) Blunted growth hormone response is associated with early relapse in alcohol-dependent patients. Alcohol Clin Exp Res 19:62–65PubMedGoogle Scholar
  63. Heinz A, Dufeu P, Kuhn S, Dettling M, Gräf K, Kürten I, Rommelspacher H, Schmidt L (1996) Psychopathological and behavioral correlates of dopaminergic sensitivity in alcohol-dependent patients. Arch Gen Psychiatry 53:1123–1128PubMedGoogle Scholar
  64. Heinz A, Ragan P, Jones D, Hommer D, Williams W, Knable M, Gorey J, Doty L, Geyer C, Lee K, Coppola R, Weinberger D, Linnoila M (1998) Reduced serotonin transporters in alcoholism. Am J Psychiatry 155:1544–1549PubMedGoogle Scholar
  65. Heinz A, Mann K, Weinberger D (2001) Serotonergic dysfunction, negative mood states, and response to alcohol. Alcohol Clin Exp Res 25:487–495PubMedGoogle Scholar
  66. Heinz A, Löber S, Georgi A, Wrase J, Hermann D, Rey E, Wellek S, Mann K (2003) Reward craving and withdrawal relief craving: assessment of different motivational pathways to alcohol intake. Alcohol Alcohol 38:35–39PubMedGoogle Scholar
  67. Heinz A, Goldman D, Gallinat J, Schumann G, Puls I (2004a) Pharmacogenetic insights to monoaminergic dysfunction in alcohol dependence. Psychopharmacology 174:561–570PubMedGoogle Scholar
  68. Heinz A, Siessmeier T, Wrase J, Hermann D, Klein S, Grüsser S, Flor H, Braus D, Buchholz H, Gründer G, Schreckenberger M, Smolka M, Rösch F, Mann K, Bartenstein P (2004b) Correlation between dopamine D-2 receptors in the ventral striatum and central processing of alcohol cues and craving. Am J Psychiatry 161:1783–1789PubMedGoogle Scholar
  69. Heinz A, Reimold M, Wrase J, Hermann D, Croissant B, Mundle G, Dohmen B, Braus D, Schumann G, Machulla H, Bares R, Mann K (2005a) Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving. Arch Gen Psychiatry 62:57–64PubMedGoogle Scholar
  70. Heinz A, Siessmeier T, Wrase J, Buchholz H, Gründer G, Kumakura Y, Cumming P, Schreckenberger M, Smolka M, Rösch F, Mann K, Bartenstein P (2005b) Correlation of alcohol craving with striatal dopamine synthesis capacity and D-2/3 receptor availability: a combined [18F]DOPA and [18F]DMFP PET Study in detoxified alcoholic patients. Am J Psychiatry 162:1515–1520PubMedGoogle Scholar
  71. Heinz A, Wrase J, Kahnt T, Beck A, Bromand Z, Grüsser S, Kienast T, Smolka M, Flor H, Mann K (2007) Brain activation elicited by affectively positive stimuli is associated with a lower risk of relapse in detoxified alcoholic subjects. Alcohol Clin Exp Res 31:1138–1147PubMedGoogle Scholar
  72. Heinz A, Beck A, Gruesser S, Grace A, Wrase J (2008) Identifying the neural circuitry of alcohol craving and relapse vulnerability. Addict Biol. 14:108–118PubMedCentralPubMedGoogle Scholar
  73. Heinz A, Beck A, Wrase J, Mohr J, Obermayer K, Gallinat J, Puls I (2009) Neurotransmitter Systems in Alcohol Dependence. Pharmacopsychiatry 42:S95–S101PubMedGoogle Scholar
  74. Hicks J, Schlegel R, Friedman R, McCarthy D (2009) Alcohol primes, expectancies, and the working self-concept. Psychol Addict Behav 23:534–538PubMedGoogle Scholar
  75. Hindmarch I, Kerr J, Sherwood N (1991) The effects of alcohol and other drugs on psychomotor performance and cognitive function. Alcohol Alcohol 26:71–79PubMedGoogle Scholar
  76. Holdstock L, King A, de Wit H (2000) Subjective and objective responses to ethanol in moderate/heavy and light social drinkers. Alcohol Clin Exp Res 24:789–794PubMedGoogle Scholar
  77. Hunt W (1983) The effect of ethanol on GABAergic neurotransmission. Neuroscience and Biobehavioral Reviews 7:87–95PubMedGoogle Scholar
  78. Ikemoto S (2007) Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res Rev 56:27–78PubMedCentralPubMedGoogle Scholar
  79. Jääskeläinen I, Schroger E, Näätänen R (1999) Electrophysiological indices of acute effects of ethanol on involuntary attention shifting. Psychopharmacology 141:16–21PubMedGoogle Scholar
  80. Jentsch J, Taylor J (1999) Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology 146:373–390PubMedGoogle Scholar
  81. Jørgensen H, Hole K (1981) Does ethanol stimulate brain opiate receptors? Studies on receptor binding and naloxone inhibition of ethanol-induced effects. Eur J Pharmacol 75:223–229PubMedGoogle Scholar
  82. Kareken D, Claus E, Sabri M, Dzemidzic M, Kosobud A, Radnovich A, Hector D, Ramchandani V, O’Connor S, Lowe M, Li T (2004) Alcohol-related olfactory cues activate the nucleus accumbens and ventral tegmental area in high-risk drinkers: preliminary findings. Alcohol Clin Exp Res 28:550–557PubMedGoogle Scholar
  83. Kiefer F, Mann K (2005) New achievements and pharmacotherapeutic approaches in the treatment of alcohol dependence. Eur J Pharmacol 526(1–3):163–171PubMedGoogle Scholar
  84. Kienast T, Heinz A (2006) Dopamine and the diseased brain. CNS Neurol Disord Drug Targets 5:109–131PubMedGoogle Scholar
  85. Kienast T, Hariri A, Schlagenhauf F, Wrase J, Sterzer P, Buchholz H, Smolka M, Gründer G, Cumming P, Kumakura Y, Bartenstein P, Dolan R, Heinz A (2008) Dopamine in amygdala gates limbic processing of aversive stimuli in humans. Nat Neurosci 11:1381–1382PubMedGoogle Scholar
  86. Knutson B, Wolkowitz O, Cole S, Chan T, Moore E, Johnson R, Terpstra J, Turner R, Reus V (1998) Selective alteration of personality and social behavior by serotonergic intervention. Am J Psychiatry 155:373–379PubMedGoogle Scholar
  87. Koelega H (1995) Alcohol and vigilance performance: A review. Psychopharmacology 118:233–249PubMedGoogle Scholar
  88. Koob G (1992) Neural Mechanisms of Drug Reinforcement. Ann N Y Acad Sci. 654:171–191PubMedGoogle Scholar
  89. Kornreich C, Philippot P, Foisy M-L, Blairy S, Raynaud E, Dan B, Hess U, Noël X, Pelc I, Verbanck P (2002) Impaired Emotional Facial Expression Recognition Is Associated With Interpersonal Problems In Alcoholism. Alcohol & Alcoholism 37:394–400Google Scholar
  90. Laakso M, Vaurio O, Savolainen L, Repo E, Soininen H, Aronen H, Tiihonen J (2000) A volumetric MRI study of the hippocampus in type 1 and 2 alcoholism. Behavioral Brain Research 109:177–186Google Scholar
  91. LeMarquand D, Pihl R, Benkelfat C (1994a) Serotonin and Alcohol Intake, Abuse, and Dependence: Clinical Evidence. Biol Psychiatry 36:326–337PubMedGoogle Scholar
  92. LeMarquand D, Pihl R, Benkelfat C (1994b) Serotonin and Alcohol Intake, Abuse, and Dependence: Findings of Animal Studies. Biol Psychiatry 36:395–421PubMedGoogle Scholar
  93. Lindenmeyer J (2001) Lieber schlau als blau. Psychologie VerlagsUnion, Verlagsgruppe Beltz, Psychologie VerlagsUnion, Verlagsgruppe BeltzGoogle Scholar
  94. Lovinger D, White G, Weight F (1989) Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243:1721–1724PubMedGoogle Scholar
  95. Lubman D, Yücel M, Pantelis C (2004) Addiction, a condition of compulsive behavior? Neuroimaging and neuropsychological evidence of inhibitory dysregulation. Addiction 99:1491–1502PubMedGoogle Scholar
  96. Lubman D, Yücel M, Kettle J, Scaffidi A, Mackenzie T, Simmons J, Allen N (2009) Responsiveness to drug cues and natural rewards in opiate addiction. Associations with later heroin use. Arch Gen Psychiatry 66:205–213Google Scholar
  97. Luciana M, Depue R, Arbisi P, Leon A (1992) Facilitation of Working Memory in Humans by a D2 Dopamine Receptor Agonist. J Cogn Neurosc 4:58–68Google Scholar
  98. Lyvers M (2000) “Loss of control” in alcoholism and drug addiction: a neuroscientific interpretation. Exp Clin Psychopharmacol 8:225–249PubMedGoogle Scholar
  99. Mann K (2004) Pharmacotherapy of Alcohol Dependence. A Review of the Clinical Data. CNS Drugs 18:485–504PubMedGoogle Scholar
  100. Marczinski C, Combs S, Fillmore M (2007) Increased sensitivity to the disinhibiting effects of alcohol in binge drinkers. Psychol Addict Behav 21:346–354PubMedGoogle Scholar
  101. Marinkovic K, Halgren E, Maltzman I (2001) Arousal-related P3a to novel auditory stimuli is abolished by moderately low alcohol dose. Alcohol and Alcoholism 36:529–539PubMedCentralPubMedGoogle Scholar
  102. Marinkovic K, Halgren E, Maltzman I (2004) Effects of alcohol on verbal processing: An ERP study. Alcoholism: Clinical and Experimental Research 28:415–423Google Scholar
  103. Martin C, Earleywine M, Musty R, Perrine M, Swift R (1993) Development and validation of the Biphasic Alcohol Effects Scale. Alcohol Clin Exp Res 17:140–146PubMedGoogle Scholar
  104. Martinez D, Gil R, Slifstein M, Hwang D, Huang Y, Perez A, Kegeles L, Talbot P, Evans S, Krystal J, Laruelle M, Abi-Dargham A (2005) Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum. Biol Psychiatry 58:779–786PubMedGoogle Scholar
  105. Modell JG, Mountz JM (1995) Focal cerebral blood flow change during craving for alcohol measured by SPECT. J Neuropsychiatry Clin Neurosci 7:15–22PubMedGoogle Scholar
  106. Molander A, Löf E, Stomberg R, Ericson M, Söderpalm B (2005) Involvement of accumbal glycine receptors in the regulation of voluntary ethanol intake in the rat. Alcohol Clin Exp Res 29:38–45PubMedGoogle Scholar
  107. Myrick H, Anton R, Li X, Henderson S, Drobes D, Voronin K, George M (2004) Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving. Neuropsychopharmacology 29:393–402PubMedGoogle Scholar
  108. Nagoshi C, Wilson J (1989) Long-term repeatability of human alcohol metabolism, sensitivity and acute tolerance. J Stud Alcohol 50:162–169PubMedGoogle Scholar
  109. Nevo I, Hamon M (1995) Neurotransmitter and neuromodulatory mechanisms involved in alcohol abuse and alcoholism. Neurochem Int 26:305–336 discussion 337-42PubMedGoogle Scholar
  110. Newlin D, Thomson J (1990) Alcohol challenge with sons of alcoholics: A critical review and analysis. Psychol Bull 108:383–402PubMedGoogle Scholar
  111. Newlin D, Thomson J (1999) Chronic tolerance and sensitization to alcohol in sons of alcoholics: II. Exp Clin Psychopharmacol 7:234–243PubMedGoogle Scholar
  112. Nixon K (2006) Alcohol and adult neurogenesis: Roles in neurodegeneration and recovery in chronic alcoholism. Hippocampus 16:287–295PubMedGoogle Scholar
  113. Olds J, Milner P (1954) Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J Comp Physiol Psychol 47:419–427PubMedGoogle Scholar
  114. Ollat H, Parvez H, Parvez S (1988) Alcohol and central neurotransmission. Neurochem Int 13:275–300PubMedGoogle Scholar
  115. Oscar-Berman M, Bowirrat A (2005) Genetic influence in emotional dysfunction and alcoholism-related brain damage. Neuropsychiatric Disease and Treatment 1:211–229PubMedCentralPubMedGoogle Scholar
  116. Oscar-Berman M, Marinkovic K (2003) Alcoholism and the brain: An overview. Alcohol Research and Health 27:125–133PubMedGoogle Scholar
  117. Oscar-Berman M, Marinkovic K (2007) Alcohol: Effects on Neurobehavioral Functions and the Brain. Neuropsychol Rev 17:239–257PubMedGoogle Scholar
  118. Park S, Kahnt T, Beck A, Cohen M, Dolan R, Wrase J, Heinz A (2010) Prefrontal cortex fails to learn from reward prediciton errors in alcohol dependence. J Neurosci 30:7749–7753PubMedCentralPubMedGoogle Scholar
  119. Paulus M, Tapert S, Schuckit M (2005) Neural activation patterns of methamphetamine-dependent subjects during decision making predict relapse. Arch Gen Psychiatry 62:761–768PubMedGoogle Scholar
  120. Pecina S, Berridge K (2005) Hedonic hot spot in nucleus accumbens shell: Where do mu-opioids cause increased hedonic impact of sweetness? J Neurosci 25:11777–11786PubMedGoogle Scholar
  121. Peterson J, Rothfleisch J, Zelazo P, Pihl R (1990) Acute alcohol intoxication and cognitive functioning. J Stud Alcohol 51:114–122PubMedGoogle Scholar
  122. Pfefferbaum A, Lim K, Desmond J, Sullivan E (1996) Thinning of the corpus callosum in older alcoholic men: A magnetic resonance imaging study. Alcoholism: Clinical and Experimental Research 20:752–757Google Scholar
  123. Pfefferbaum A, Sullivan E, Mathalon D, Lim K (1997) Frontal lobe volume loss observed with magnetic resonance imaging in older chronic alcoholics. Alcohol Clin Exp Res. 21:521–529PubMedGoogle Scholar
  124. Pfefferbaum A, Adalsteinsson E, Sullivan E (2006) Dysmorphology and microstructural degradation of the corpus callosum: Interaction of age and alcoholism. Neurobiology of Aging 27:994–1009PubMedGoogle Scholar
  125. Philippot P, Kornreich C, Blairy S, Baert I, Den Dulk A, Le Bon O, Streel E, Hess U, Pelc I, Verbanck P (1999) Alcoholics’ Deficit in the Decoding of Emotional Facial Expression. Alcoholism: Clinical and Experimental Research 23:1031–1038Google Scholar
  126. Pihl R, Peterson J, Lau M (1993) A biosocial model of the alcohol-aggression relationship. J Stud Alcohol Suppl 11:128–139PubMedGoogle Scholar
  127. Pohorecky L (1977) Biphasic action of ethanol. Biobehavioral Reviews 1:231–240Google Scholar
  128. Ramchandani VA, Umhau J, Pavon FJ, Ruiz-Velasco V, Margas W, Sun H, Damadzic R, Eskay R, Schoor M, Thorsell A, Schwandt ML, Sommer WH, George DT, Parsons LH, Herscovitch P, Hommer D, Heilig M (2010) A genetic determinant of the striatal dopamine response to alcohol in men. Mol Psychiatry. May 18. [Epub ahead of print]Google Scholar
  129. Ray L, MacKillop J, Leventhal A, Hutchison K (2009) Catching the alcohol buzz: an examination of the latent factor structure of subjective intoxication. Alcohol Clin Exp Res 33:2154–2161PubMedCentralPubMedGoogle Scholar
  130. Robbins T, Everitt B (2002) Limbic-striatal memory systems and drug addiction. Neurobiol Learn Mem 78:625–636PubMedGoogle Scholar
  131. Robbins T, Cador M, Taylor J, Everitt B (1989) Limbic-striatal interactions in reward-related processes. Neurosci Biobehav Rev 13:155–162PubMedGoogle Scholar
  132. Robinson T, Berridge K (1993) The neural basis of drug craving - an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18:247–291PubMedGoogle Scholar
  133. Rosenbloom M, Sullivan E, Pfefferbaum A (2003) Using magnetic resonance imaging and diffusion tensor imaging to assess brain damage in alcoholics. Alcohol Research and Health 27:146–152PubMedGoogle Scholar
  134. Rossetti Z, Melis F, Carboni S, Gessa G (1992) Dramatic depletion of mesolimbic extracellular dopamine after withdrawal from morphine, alcohol or cocaine - a common neurochemical substrate for drug-dependence. Ann N Y Acad Sci. 654:513–516PubMedGoogle Scholar
  135. Salloum JB, Ramchandani VA, Bodurka J, Rawlings R, Momenan R, George D, Hommer DW (2007) Blunted rostral anterior cingulate response during a simplified decoding task of negative emotional facial expressions in alcoholic patients. Alcohol Clin Exp Res 31:1490-1504PubMedGoogle Scholar
  136. Schneider F, Habel U, Wagner M, Franke P, Salloum JB, Shah NJ, Toni I, Sulzbach C, Hönig K, Maier W, Gaebel WKZ (2001) Subcortical correlates of craving in recently abstinent alcoholic patients. Am J Psychiatry 158:1075–1083PubMedGoogle Scholar
  137. Schuckit M, Smith T (1996) An 8-year follow-up of 450 sons of alcoholic and control subjects. Arch Gen Psychiatry 53:202–210PubMedGoogle Scholar
  138. Schuckit M, Smith T, Kalmijn J (2004) The search for genes contributing to the low level of response to alcohol: patterns of findings across studies. Alcohol Clin Exp Res 28:1449–1458PubMedGoogle Scholar
  139. Schulte T, Sullivan E, Muller-Oehring E, Adalsteinsson E, Pfefferbaum A (2005) Corpus callosal microstructural integrity influences interhemispheric processing: A diffusion tensor imaging study. Cerebral Cortex 15:1384–1392PubMedGoogle Scholar
  140. Schultz W, Dayan P, Montague P (1997) A neural substrate of prediction and reward. Science 275:1593–1599PubMedGoogle Scholar
  141. Shalev U, Highfield D, Yap J, Shaham Y (2000) Stress and relapse to drug seeking in rats: studies on the generality of the effect. Psychopharmacology 150:337–346PubMedGoogle Scholar
  142. Söderpalm B, Löf E, Ericson M (2009) Mechanistic studies of ethanol’s interaction with the mesolimbic dopamine reward system. Pharmacopsychiatry 42:S87–S94PubMedGoogle Scholar
  143. Spanagel R, Herz A, Shippenberg T (1992) Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci 89:2046–2050PubMedGoogle Scholar
  144. Stephens DN, Duka T, Crombag HS, Cunningham CL, Heilig M, Crabbe JC (2010) Reward sensitivity: issues of measurement, and achieving consilience between human and animal phenotypes. Addict Biol 15(2):145–168PubMedGoogle Scholar
  145. Sullivan E (2000) Neuropsychological vulnerability to alcoholism: Evidence from neuroimaging studies. In: Noronha A, Eckardt M, Warren K (eds) Review of NIAAA’s neuroscience and behavioral research (Monograph No. 34. NIAAA, Bethesda, MD, pp 473–508Google Scholar
  146. Sullivan E, Marsh L, Mathalon D, Lim K, Pfefferbaum A (1995) Anterior hippocampal volume deficits in nonamnesic, aging chronic alcoholics. Alcoholism: Clinical and Experimental Research 19:110–122Google Scholar
  147. Tapert S, Brown G, Baratta M, Brown S (2004) FMRI BOLD response to alcohol stimuli in alcohol dependent young women. Addict Behav 29:33–50PubMedGoogle Scholar
  148. Ticku M (1989) Ethanol and the benzodiazepine-GABA-receptor-ionophore complex. Experientia 45:413–418PubMedGoogle Scholar
  149. Tiffany S (1990) A cognitive model of drug urges and drug-use behavior–role of automatic and nonautomatic processes. Psychol Rev 97:147–168PubMedGoogle Scholar
  150. Tiplady B, Franklin N, Scholey A (2004) Effect of ethanol on judgments of performance. Br J Psychol 95:105–118PubMedGoogle Scholar
  151. Tobler T, Fiorillo C, Schultz W (2005) Adaptive coding of reward value by dopamine neurons. Science 307:1642–1645PubMedGoogle Scholar
  152. Tsai G, Gastfriend D, Coyle J (1995) The glutamatergic basis of human alcoholism. Am J Psychiatry 152:332–340PubMedGoogle Scholar
  153. Uekermann J, Daum I (2008) Social cognition in alcoholism: a link to prefrontal cortex dysfunction? Addiction 103:726–735PubMedGoogle Scholar
  154. Uhart M and Wand G (2008) Stress, alcohol and drug interaction: an update of human research. Addict Biol. 14:43–64PubMedCentralPubMedGoogle Scholar
  155. Uhl G, Blum K, Noble E, Smith S (1993) Substance abuse vulnerability and D2 receptor genes. Trends Neurosci 16:83–88PubMedGoogle Scholar
  156. Valenzuela C (1997) Alcohol and Neurotransmitter Intractions. Alcohol Health & Research World 21:144–148Google Scholar
  157. van Erp A, Miczek K (2007) Increased accumbal dopamine during daily alcohol consumption and subsequent aggressive behavior in rats. Psychopharmacology 191:679–688PubMedGoogle Scholar
  158. Vanderschuren L, Di Ciano P, Everitt B (2005) Involvement of the dorsal striatum in cue-controlled cocaine seeking. J Neurosci 25:8665–8670PubMedGoogle Scholar
  159. Vengeliene V, Leonardi-Essmann F, Sommer WH, M Marston H, Spanagel R (2010) Glycine Transporter-1 Blockade Leads to Persistently Reduced Relapse-like Alcohol Drinking in Rats. Biol Psychiatry. Jul 22. [Epub ahead of print]Google Scholar
  160. Volkow N, Hitzmann R, Wolf A, Logan J, Fowler J, Christman D, Dewey S, Schlyer D, Burr G, Vitkun S, Hirschowitz J (1990) Acute Effects of Ethanol on Regional Brain Glucose Metabolism and Transport. Psychiatry Research: Neuroimaging 35:39–48PubMedGoogle Scholar
  161. Volkow N, Wang G, Fowler J, Logan J, Hitzemann R, Ding Y, Pappas N, Shea C, Piscani K (1996) Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcohol Clin Exp Res 20:1594–1598PubMedGoogle Scholar
  162. Volkow N, Wang G, Fowler J, Logan J, Gatley S, Hitzemann R, Chen A, Dewey S, Pappas N (1997) Decreased striatal dopaminergic responsiveness in detoxified cocainedependent subjects. Nature 386:830–833PubMedGoogle Scholar
  163. Volkow N, Wang G, Fowler J, Logan J, Gatley S, Gifford A, Hitzemann R, Ding Y, Pappas N (1999) Prediction of reinforcing responses to psychostimulants in humans by brain dopamine D2 receptor levels. Am J Psychiatry 156:1440–1443PubMedGoogle Scholar
  164. Volkow N, Chang L, Wang G, Fowler J, Ding Y, Sedler M, Logan J, Franceschi D, Gatley J, Hitzemann R, Gifford A, Wong C, Pappas N (2001) Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex. Am J Psychiatry 158:2015–2021PubMedGoogle Scholar
  165. Volkow N, Fowler J, Wang G, Swanson J (2004) Dopamine in drug abuse and addiction: results from imaging studies and treatment implications. Molecular Psychiatry 9:557–569PubMedGoogle Scholar
  166. Volkow N, Wang G, Begleiter H, Porjesz B, Fowler J, Telang F, Wong C, Ma Y, Logan J, Goldstein R, Alexoff D, Thanos P (2006) High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors. Arch Gen Psychiatry 63:999–1008PubMedGoogle Scholar
  167. Volpicelli J, Watson N, King A, Sherman C, O’Brien C (1995) Effect of naltrexone on alcohol “high” in alcoholics. Am J Psychiatry 152Google Scholar
  168. Wang G, Volkow N, Franceschi D, Fowler J, Thanos P, Scherbaum N, Pappas N, Wong C, Hitzemann R, Felder C (2000) Regional brain metabolism during alcohol intoxication. Alcohol Clin Exp Res 24:822–829PubMedGoogle Scholar
  169. Weiss F (2005) Neurobiology of craving, conditioned reward and relapse. Curr Opin Pharmacol. 5:9–19PubMedGoogle Scholar
  170. WHO (2007) World health organization expert committee on problems related to alcohol consumption. 2. World Health Organization, Geneva, SwitzerlandGoogle Scholar
  171. Williams A (1966) Social drinking, anxiety, and depression. J Pers Soc Psychol. 3:689–693PubMedGoogle Scholar
  172. Williams G, Goldman-Rakic P (1995) Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 376:572–575PubMedGoogle Scholar
  173. Wise R (1982) Neuroleptics and operant behavior: the anhedonia hypothesis. Behav Brain Sci 5:39–87Google Scholar
  174. Wise R (1996) Neurobiology of addiction. Curr Opin Pharmacol. 6:243–251Google Scholar
  175. Wise R (2002) Brain Reward Circuitry: Insights from Unsensed Incentives. Neuron 36:229–240PubMedGoogle Scholar
  176. Wise R, Rompre P (1989) Brain Dopamine and Reward. Annu. Rev. Psychol. 40:191–225PubMedGoogle Scholar
  177. Wong D, Kuwabara H, Schretlin D, Bonson K, Zhou Y, Nandi A, Brasic J, Kimes A, Maris M, Kumar A, Contoreggi C, Links J, Ernst M, Rousset O, Zukin S, Grace A, Rohde C, Jasinski D, Gjedde A, London E (2006) Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving. Neuropsychopharmacology 31:2716–2727PubMedGoogle Scholar
  178. Wrase J, Grüsser S, Klein S, Diener C, Hermann D, Flor H, Mann K, Braus D, Heinz A (2002) Development of alcohol-associated cues and cue-induced brain activation in alcoholics. Eur Psychiatry 17:287–291PubMedGoogle Scholar
  179. Wrase J, Grüsser S, Heinz A (2006) Cue-induced alcohol craving. Neurobiological correlates and clinical relevance. Nervenarzt 77:1051–1063PubMedGoogle Scholar
  180. Wrase J, Schlagenhauf F, Kienast T, Wüstenberg T, Bermpohl F, Kahnt T, Beck A, Ströhle A, Juckel G, Knutson B, Heinz A (2007) Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics. Neuroimage 35:787–794PubMedGoogle Scholar
  181. Yoshimoto K, McBride W (1992) Regulation of nucleus accumbens dopamine release by the dorsal raphe nucleus in the rat. Neurochem Res 17:401–407PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Psychiatry and PsychotherapyCharité Universitätsmedizin BerlinBerlinGermany

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